The immune monitoring program of the Department of Immunology in LUMC, led by Prof. Jacques J.M. van Dongen, MD, PhD, consists of translational research aiming at unravelling cellular, functional and molecular genetic processes during normal and abnormal immune cell development (differentiation) and maturation, and on the development and clinical evaluation of new diagnostic strategies and techniques in medical immunology.
Maturation of hematopoietic cells into different types of immune cells is a complex process. Insight into normal differentiation and maturation processes makes it possible to recognize atypical and aberrant patterns that may be related to immune diseases or other disruptions of the immune system. This knowledge forms the basis for the development of new methods for diagnosis, classification and monitoring of various immune diseases, such as autoimmune diseases, inflammatory processes, allergies, immunodeficiencies, and hematological malignancies.
The program particularly supports monitoring of immune cell populations during the disease course and during treatment, such as immunotherapies with antibodies, checkpoint inhibitors and cellular therapies (including transplantation and gene therapy), as well as vaccination and cancer treatment.
The research within the immune monitoring program contributes to diagnostic patient care and supports personalized treatment, in which treatment strategies are optimized based on the results of immune monitoring.
Figure 1. Composition of Immune Monitoring team at Immunology in LUMC. Researchers : Jacques J.M. van Dongen, Cristina I. Teodosio, Magda A. Berkowska, Mihaela Zlei, Paula Díez Garcia, and Indu Khatri; PhD students: Wouter B.L. van den Bossche, Annieck Diks, Kyra van der Pan, and Anniek de Jager; Technicians: Gita Naber, Alita van der Sluijs, Sandra de Bruin, Sandra Vloemans, Rick Groenland, Bas de Mooij, Fenna de Bie, Inge de Laat, and Sara Kassem; Project support team: Marieke Bitter, Bart Lubbers, and Alyssa van der Meij.
Research line 1: Immune monitoring and Medical immunology
Lead: Mihaela Zlei and Jacques J.M. van Dongen
To support translational research projects, diagnostics and clinical studies, continuous effort is made to develop, optimize and standardize new immune monitoring techniques. For example, by mapping the immune system more accurately with molecular and cellular techniques, the disease status and the effects of a treatment can be investigated with increasing precision. Innovation within these and other research lines within the immune monitoring program therefore directly contributes to translational research.
Important areas of application include diseases of the immune system and immunotherapies. This means that immune monitoring is relevant for a large number of medical fields. Therefore many collaborations with clinical departments of LUMC are included in this research line. In addition, immune monitoring is used to contribute to clinical studies in collaboration with pharmaceutical industry.
In order to ensure high-quality and reproducible research, and to support the implementation of immune monitoring techniques in laboratories around the world, standardization of these techniques in an international, multi-center context is a priority, such as within the EuroFlow and EuroClonality research consortia. The LUMC immune monitoring team is continuously contributing to these research consortia (www.EuroFlow.org and www.EuroClonality.org).
Figure 2. Multidimensional flow cytometric analysis of the monocyte-dendritic cell compartment (left) and the blood B-cell/plasma cell compartment (right).
Research line 2: Monitoring of cancer via tissue macrophages: ERC-supported TiMaScan project
Lead: Cristina Teodosio, Paula Díez and Jacques J.M. van Dongen
PhD students: Wouter B.L. van den Bossche, Kyra van der Pan, Anniek de Jager
The immune system consists of many different types of immune cells with various functions. In order to optimally distinguish these cells from each other and to understand their biological role, methods are developed to measure the differentiation and maturation of immune cells in as much detail as possible. These methods are subsequently used to detect and monitor diseases.
Within the TiMaScan project, the detection of monocytes and macrophages is the main focus. Macrophages clean up pathogens and damaged and dead cells throughout the body. By developing methods to measure tissue macrophages that have incorporated cancer-specific protein fragments, we try to make earlier diagnosis and better monitoring of cancer treatment possible. This is done with advanced techniques, in particular flow cytometric analysis of circulating tissue macrophages.
The TiMaScan project is supported by the European Commission through the ERC Advanced grant of Prof. van Dongen (ERC-AdG 695655) called TiMaScan.
Research line 3: Monitoring of the immune response after vaccination
Lead: Magda Berkowska, Indu Khatri and Jacques J.M. van Dongen
PhD student: Annieck Diks
In this research line, immune monitoring is used to gain better insight into the immune response after vaccination and to use this knowledge to understand and improve the effectiveness of vaccinations, i.e. to understand the mechanisms of protection, memory, and waning of the immune response to vaccines.
Vaccination, or induction of an immune response against a pathogen by the administration of the weakened or dead pathogen or of isolated antigens, causes a complex dynamic change in the immune system. Many different cell populations are involved in this process. By visualizing the different populations of immune cells as detailed as possible, we can learn more about the involvement of these populations in an immune response. With this knowledge we can better predict the effectiveness of vaccinations and contribute to the development of more effective vaccinations.
A large project within this research line is PERISCOPE. This project focuses on vaccination against Bordetella pertussis (whooping cough), and aims to accelerate the development of a more effective and safer vaccine against this disease by identifying long-term biomarkers of immunity. Immune monitoring techniques are developed and applied to map the response of the immune system to vaccination against or infection with Bordetella pertussis. One example is the development of antibody panels for flow cytometry with the aim to identify large numbers of subpopulations of e.g. monocytes, T cells and B cells. In addition, antigen-specific B cells are examined in more detail on the basis of single cell RNA sequencing to understand the selection processes in antigen-specific antibody repertoire.
The PERISCOPE Consortium is supported by the European Innovative Medicines Initiative (IMI) and the Bill & Melinda Gates Foundation.